NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (NUS), 21 Lower Kent Ridge Rd, 119077, Singapore.
Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, 138673, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level, 7119228, Singapore; Singapore Eye Research Institute (SERI), The Academia, 20 College Road, Level 6 Discovery Tower, 169856, Singapore.
Biomaterials. 2022 Jan;280:121262. doi: 10.1016/j.biomaterials.2021.121262. Epub 2021 Nov 17.
Vitreous endotamponades play essential roles in facilitating retina recovery following vitreoretinal surgery, yet existing clinically standards are suboptimal as they can cause elevated intra-ocular pressure, temporary loss of vision, and cataracts while also requiring prolonged face-down positioning and removal surgery. These drawbacks have spurred the development of next-generation vitreous endotamponades, of which supramolecular hydrogels capable of in-situ gelation have emerged as top contenders. Herein, we demonstrate thermogels formed from hyper-branched amphiphilic copolymers as effective transparent and biodegradable vitreous endotamponades for the first time. These hyper-branched copolymers are synthesised via polyaddition of polyethylene glycol, polypropylene glycol, poly(ε-caprolactone)-diol, and glycerol (branch inducing moiety) with hexamethylene diisocyanate. The hyper-branched thermogels are injected as sols and undergo spontaneous gelation when warmed to physiological temperatures in rabbit eyes. We found that polymers with an optimal degree of hyper-branching showed excellent biocompatibility and was able to maintain retinal function with minimal atrophy and inflammation, even at absolute molecular weights high enough to cause undesirable in-vivo effects for their linear counterparts. The hyper-branched thermogel is cleared naturally from the vitreous through surface hydrogel erosion and negates surgical removal. Our findings expand the scope of polymer architectures suitable for in-vivo intraocular therapeutic applications beyond linear constructs.
玻璃体填充物在玻璃体视网膜手术后促进视网膜恢复方面起着至关重要的作用，但现有的临床标准并不理想，因为它们会导致眼内压升高、暂时失明和白内障，同时还需要长时间的面朝下体位和取出手术。这些缺点促使人们开发了下一代玻璃体填充物，其中能够原位凝胶化的超分子水凝胶已成为首选。在此，我们首次展示了由超支化两亲性共聚物形成的热凝胶作为有效的透明和可生物降解的玻璃体填充物。这些超支化共聚物是通过聚乙二醇、聚丙二醇、聚（ε-己内酯）-二醇和甘油（支化诱导部分）与六亚甲基二异氰酸酯的加成聚合合成的。超支化热凝胶以溶胶形式注射，并在兔眼升温至生理温度时自发凝胶化。我们发现，具有最佳超支化程度的聚合物表现出优异的生物相容性，能够保持视网膜功能，最小化萎缩和炎症，即使分子量高到足以对其线性对应物产生不良的体内效应。超支化热凝胶通过表面水凝胶侵蚀自然从玻璃体中清除，无需手术切除。我们的发现将适用于体内眼内治疗应用的聚合物结构范围扩展到了线性结构之外。
